Segregating variation in the transcriptome: cis regulation and additivity of effects.
ABSTRACT Properties of genes underlying variation in complex traits are largely unknown, especially for variation that segregates within populations. Here, we evaluate allelic effects, cis and trans regulation, and dominance patterns of transcripts that are genetically variable in a natural population of Drosophila melanogaster. Our results indicate that genetic variation due to the third chromosome causes mainly additive and nearly additive effects on gene expression, that cis and trans effects on gene expression are numerically about equal, and that cis effects account for more genetic variation than do trans effects. We also evaluated patterns of variation in different functional categories and determined that genes involved in metabolic processes are overrepresented among variable transcripts, but those involved in development, transcription regulation, and signal transduction are underrepresented. However, transcripts for proteins known to be involved in protein-protein interactions are proportionally represented among variable transcripts.
Article: From QTL to candidate gene: genetical genomics of simple and complex traits in potato using a pooling strategy.[show abstract] [hide abstract]
ABSTRACT: Utilization of the natural genetic variation in traditional breeding programs remains a major challenge in crop plants. The identification of candidate genes underlying, or associated with, phenotypic trait QTLs is desired for effective marker assisted breeding. With the advent of high throughput -omics technologies, screening of entire populations for association of gene expression with targeted traits is becoming feasible but remains costly. Here we present the identification of novel candidate genes for different potato tuber quality traits by employing a pooling approach reducing the number of hybridizations needed. Extreme genotypes for a quantitative trait are collected and the RNA from contrasting bulks is then profiled with the aim of finding differentially expressed genes. We have successfully implemented the pooling strategy for potato quality traits and identified candidate genes associated with potato tuber flesh color and tuber cooking type. Elevated expression level of a dominant allele of the beta-carotene hydroxylase (bch) gene was associated with yellow flesh color through mapping of the gene under a major QTL for flesh color on chromosome 3. For a second trait, a candidate gene with homology to a tyrosine-lysine rich protein (TLRP) was identified based on allele specificity of the probe on the microarray. TLRP was mapped on chromosome 9 in close proximity to a QTL for potato cooking type strengthening its significance as a candidate gene. Furthermore, we have performed a profiling experiment targeting a polygenic trait, by pooling individual genotypes based both on phenotypic and marker data, allowing the identification of candidate genes associated with the two different linkage groups. A pooling approach for RNA-profiling with the aim of identifying novel candidate genes associated with tuber quality traits was successfully implemented. The identified candidate genes for tuber flesh color (bch) and cooking type (tlrp) can provide useful markers for breeding schemes in the future. Strengths and limitations of the approach are discussed.BMC Genomics 03/2010; 11:158. · 4.07 Impact Factor
Article: Candidate genes detected in transcriptome studies are strongly dependent on genetic background.[show abstract] [hide abstract]
ABSTRACT: Whole genome transcriptomic studies can point to potential candidate genes for organismal traits. However, the importance of potential candidates is rarely followed up through functional studies and/or by comparing results across independent studies. We have analysed the overlap of candidate genes identified from studies of gene expression in Drosophila melanogaster using similar technical platforms. We found little overlap across studies between putative candidate genes for the same traits in the same sex. Instead there was a high degree of overlap between different traits and sexes within the same genetic backgrounds. Putative candidates found using transcriptomics therefore appear very sensitive to genetic background and this can mask or override effects of treatments. The functional importance of putative candidate genes emerging from transcriptome studies needs to be validated through additional experiments and in future studies we suggest a focus on the genes, networks and pathways affecting traits in a consistent manner across backgrounds.PLoS ONE 01/2011; 6(1):e15644. · 4.09 Impact Factor
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ABSTRACT: The fitness consequences of inbreeding have attracted the attention of biologists since the time its harmful effects were first recognized by Charles Darwin. Although inbreeding depression has been a central theme in biological research for over a century, little is known about its underlying molecular basis. With the generation of vast amounts of DNA sequence information and the advent of microarrays we are now able to describe biological processes from a total genomic perspective. This article reviews the ways in which microarrays have advanced our understanding of the molecular basis of inbreeding depression, including our first look at the number of genes associated with inbreeding depression, which genes or functional classes of genes are responsible for the decrease in fitness associated with inbreeding, the underlying cause of inbreeding depression—overdominance or partially recessive deleterious alleles—and environmental influences on gene-expression patterns.BioScience 04/2010; · 4.62 Impact Factor